Genome‐wide identification of <i>Listeria monocytogenes</i> CodY‐binding sites

Biswas, Ratna; Sonenshein, Abraham L.; Belitsky, Boris R.

doi:10.1111/mmi.14449

Cited by 15 publications

(17 citation statements)

References 69 publications

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“…aureus UAMS-1 ( Figure 2C). Furthermore, the S. aureus TCH1516 CodY binding motif is similar with the CodY binding motif (AATTTTCWGAATATTCWGAAAATT) reported in Listeria monocytogenes and Bacillus subtilis (18,19). These results suggest that CodY likely has a conserved DNA-binding domain in Gram-positive bacteria ( Supplementary Figure 1).…”

Section: Identification Of the Cody-binding Motif In S Aureus Tch1516supporting

confidence: 77%

Elucidating the CodY regulon inStaphylococcus aureusUSA300 substrains

Gao

Poudel

Seif

et al. 2021

Preprint

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CodY is a conserved broad acting transcription factor that regulates the expression of genes related to amino acid metabolism and virulence in methicillin-resistant Staphylococcus aureus (MRSA). CodY target genes have been studied by using in vitro DNA affinity purification and deep sequencing (IDAP-Seq). Here we performed the first in vivo determination of CodY target genes using a novel CodY monoclonal antibody in established ChIP-exo protocols. Our results showed, 1) the same 135 CodY promoter binding sites regulating 165 target genes identified in two closely related virulent S. aureus USA300 TCH1516 and LAC strains; 2) The differential binding intensity for the same target genes under the same conditions was due to sequence differences in the same CodY binding site in the two strains; 3) Based on transcriptomic data, a CodY regulon comprising 72 target genes that are differentially regulated relative to a CodY deletion strain, representing genes that are mainly involved in amino acid transport and metabolism, inorganic ion transport and metabolism, transcription and translation, and virulence; and 4) CodY systematically regulated central metabolic flux to generate branched-chain amino acids (BCAAs) by mapping the CodY regulon onto a genome-scale metabolic model of S. aureus. Our study performed the first system-level analysis of CodY in two closely related USA300 TCH1516 and LAC strains giving new insights into the similarities and differences of CodY regulatory roles between the closely related strains.ImportanceWith the increasing availability of whole genome sequences for many strains within the same pathogenic species, a comparative analysis of key regulators is needed to understand how the different strains uniquely coordinate metabolism and expression of virulence. To successfully infect the human host, Staphylococcus aureus USA300 relies on the transcription factor CodY to reorganize metabolism and express virulence factors. While CodY is a known key transcription factor, its target genes are not characterized on a genome-wide basis. We performed a comparative analysis to describe the transcriptional regulation of CodY between two dominant USA300 strains. This study motivates the characterization of common pathogenic strains and an evaluation of the possibility of developing specialized treatments for major strains circulating in the population.

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Section: Identification Of the Cody-binding Motif In S Aureus Tch1516supporting

confidence: 77%

Elucidating the CodY regulon inStaphylococcus aureusUSA300 substrains

Gao

Poudel

Seif

et al. 2021

Preprint

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“…A genome wide analysis of the CodY regulon identified sigB as one of the genes that is also directly regulated by CodY, indicating that CodY may promote prfA transcription by at least two different mechanisms: directly via binding to the prfA gene and indirectly by relieving sigB repression (Lobel and Herskovits, 2016). However, in vitro binding of CodY to the 5' coding region of prfA is very weak, suggesting that other indirect mechanisms are likely to be involved in CodY-mediated prfA activation (Biswas et al, 2020).…”

Section: σ B -Dependent Stress Resistance Role In Virulencementioning

confidence: 99%

The σB-Mediated General Stress Response of Listeria monocytogenes: Life and Death Decision Making in a Pathogen

2020

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Sensing and responding to environmental cues is critical for the adaptability and success of the food-borne bacterial pathogen Listeria monocytogenes. A supramolecular multiprotein complex known as the stressosome, which acts as a stress sensing hub, is responsible for orchestrating the activation of a signal transduction pathway resulting in the activation of σ B , the sigma factor that controls the general stress response (GSR). When σ B is released from the anti-sigma factor RsbW, a rapid up-regulation of the large σ B regulon, comprised of ≥ 300 genes, ensures that cells respond appropriately to the new environmental conditions. A diversity of stresses including low pH, high osmolarity, and blue light are known to be sensed by the stressosome, resulting in a generalized increase in stress resistance. Appropriate activation of the stressosome and deployment of σ B are critical to fitness as there is a trade-off between growth and stress protection when the GSR is deployed. We review the recent developments in this field and describe an up-to-date model of how this sensory organelle might integrate environmental signals to produce an appropriate activation of the GSR. Some of the outstanding questions and challenges in this fascinating field are also discussed.

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“…All three major targets of L. monocytogenes GlnR, the glnRA and amtB glnK operons and the gdhA gene, were reported (at least under some growth conditions) to be under the control of CodY, an important global regulator of metabolism and virulence in most low-GϩC Gram-positive bacteria (13,45). To test the possible interaction between GlnR and CodY, we determined the expression of these genes in a codY null mutant and a (14). The lack of CodY regulation also indicates that the CodY-binding site found within the coding sequence of glnR (14) does not contribute significantly to regulation.…”

Section: Resultsmentioning

confidence: 99%

“…Two related transcriptional regulators, TnrA and GlnR, and the global transcriptional regulator CodY are responsible for the regulation of many genes of nitrogen metabolism in a model low-GϩC Gram-positive bacterium, Bacillus subtilis (9,10). The L. monocytogenes CodY regulon and the role of CodY in virulence have been characterized in some detail (11)(12)(13)(14). However, no genome-wide knowledge of the roles of TnrA or GlnR homologs in regulation of gene expression and virulence exists in L. monocytogenes.…”

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confidence: 99%

Role of GlnR in Controlling Expression of Nitrogen Metabolism Genes in Listeria monocytogenes

2020

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Listeria monocytogenes is a fastidious bacterial pathogen that can utilize only a limited number of nitrogen sources for growth. Both glutamine and ammonium are common nitrogen sources used in listerial defined growth media, but little is known about the regulation of their uptake or utilization. The functional role of L. monocytogenes GlnR, the transcriptional regulator of nitrogen metabolism genes in low G+C Gram-positive bacteria, was determined using RNA-Seq and real-time RT-PCR experiments. The GlnR regulon included transcriptional units involved in ammonium transport (amtB glnK) and biosynthesis of glutamine (glnRA) and glutamate (gdhA) from ammonium. As in other bacteria, GlnR proved to be an autoregulatory repressor of the glnRA operon. Unexpectedly, GlnR was most active during growth with ammonium as the nitrogen source and less active in the glutamine medium, apparently because listerial cells perceive growth with glutamine as a nitrogen-limiting condition. Therefore, paradoxically, expression of the glnA gene, encoding glutamine synthetase, was highest in the glutamine medium. For the amtB glnK operon, GlnR served as both a negative regulator in the presence of ammonium and a positive regulator in the glutamine medium. The gdhA gene was subject to a third mode of regulation that apparently required an elevated level of GlnR for repression. Finally, activity of glutamate dehydrogenase encoded by the gdhA gene appeared to correlate inversely with expression of gltAB, the operon that encodes the other major glutamate-synthesizing enzyme, glutamate synthase. Both gdhA and amtB were also regulated, in a negative manner, by the global transcriptional regulator CodY. IMPORTANCE L. monocytogenes is a widespread foodborne pathogen. Nitrogen-containing compounds, such as the glutamate-containing tripeptide, glutathione, and glutamine, have been shown to be important for expression of L. monocytogenes virulence genes. In this work, we showed that a transcriptional regulator, GlnR, controls expression of critical listerial genes of nitrogen metabolism that are involved in ammonium uptake and biosynthesis of glutamine and glutamate. A different mode of GlnR-mediated regulation was found for each of these three pathways.

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Genome‐wide identification of Listeria monocytogenes CodY‐binding sites

Cited by 15 publications

References 69 publications

Elucidating the CodY regulon inStaphylococcus aureusUSA300 substrains

Elucidating the CodY regulon inStaphylococcus aureusUSA300 substrains

The σB-Mediated General Stress Response of Listeria monocytogenes: Life and Death Decision Making in a Pathogen

Role of GlnR in Controlling Expression of Nitrogen Metabolism Genes in Listeria monocytogenes

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